This application proposes a training plan to develop Simeon A. Boyadjiev, M.D., into an independent clinical scientist, expert in clinical and molecular genetics and genetic epidemiology. Since October 1997, Dr. Boyadjiev is a board certified Pediatrician and as of September 1999, he is certified as a Clinical Geneticist by The American Board of Medical Genetics. The Johns Hopkins University is exceptionally well suited to serve as his training site. The training program will consist of mentored research experience, multi-disciplinary conferences, and advanced course work, leading to a Master of Public Health degree in Human Genetics and Genetic Epidemiology. Mentored research will be conducted as a member of the Center for Craniofacial Development and Disorders (CCDD) under his primary mentor Prof. Ethylin Wang Jabs, M.D., member of the Institute of Genetic Medicine and Director of CCDD, and co-mentor Terri Beaty, Ph.D., Professor of Epidemiology and Director of the Human Genetics and Genetic Epidemiology program at the School of Hygiene and Public Health. Prof. Garry Cutting, M.D., Director of the DNA Diagnostic Laboratory at Johns Hopkins will serve as a co-mentor and direct Dr. Boyadjiev's training in Clinical Molecular Genetics during the first year of the award. The research project will be conducted through clinic-based study of patients and utilize molecular and epidemiologic methodologies. The specific aims are: 1) to characterize isolated and syndromic forms of craniosynostosis; 2) to collect a sufficient number of case-parent trios with isolated craniosynostosis in order to achieve sufficient statistical power; 3) to identify and utilize new and existing single nucleotide polymorphisms (SNP) in order to establish linkage to specific chromosomal regions; 4) to identify and test candidate genes and loci for mutations and allelic associations; 5) to identify environmental risk factors for various subtypes of craniosynostosis; and 6) to develop an efficient model that can be applied toward the analysis of genetic and non-genetic causes of craniosynostosis as well as other congenital anomalies with complex inheritance.